Therapeutically antihypertensive agents

Oates, J.A., Antihypertensive agents and the drug therapy of hypertension, in Goodman and Gilman s The Pharmacological Basis of Therapeutics, 9th ed., Hardman, J.G. and Limbird, L.E., Eds., McGraw-Hill, New York, 1996, chap. 33. 

Minoxidil may produce serious adverse effects. It can cause pericardial effusion, occasionally progressing to tamponade it can exacerbate angina pectoris. Reserve for hypertensive patients who do not respond adequately to maximum therapeutic doses of a diuretic and 2 other antihypertensive agents. 

Mechanism of Action An antihypertensive agent that stimulates central inhibitory alpha-adrenergic receptors, lowers arterial pressure, and reduces plasma renin activity. Therapeutic Effect Reduces BP. 

Mechanism of Action An antianginal and antihypertensive agent that inhibits calcium ion movement across cell membranes, depressing contraction of cardiac and vascular smooth muscle. Therapeutic Effect Increases heart rate and cardiac output. Decreases systemic vascular resistance and BP. 

Mechanism of Action An antihypertensive and antianginal, antiarrhythmic, and antihypertensive agent that inhibits calcium ion entry across cardiac and vascular smooth-muscle cell membranes. This action causes the dilation of coronary arteries, peripheral arteries, and arterioles. Therapeutic Effect Decreases heart rate and myocardial contractility and slows SA and AV conduction. Decreases total peripheral vascular resistance by vasodilation. 

Clonidine (4.42) is an ttj agonist. Therapeutically, clonidine is a central antihypertensive agent, which may perhaps act on the baroreceptor (blood pressure sensor) reflex pathway, on cardiovascular centers in the medulla, and also peripherally. As is evident... 

Oates JA, Brown NJ. Antihypertensive agents and the drug treatment of hypertension. In Hardman JG, et al, eds. The Pharmacological Basis of Therapeutics. 10th ed. New York McGraw-Hill 2001. 

As noted above, serotonin synthesis can be inhibited by p-chlorophenylalanine andp-chloroamphetamine. However, these agents are too toxic for general use. Storage of serotonin can be inhibited by the use of reserpine, but the sympatholytic effects of this drug (see Chapter 11 Antihypertensive Agents) and the high levels of circulating serotonin that result from release prevent its use in carcinoid. Therefore, receptor blockade is the major approach to therapeutic limitation of serotonin effects. 

Individuals may show an undesired excessive therapeutic response (e.g., becoming hypotensive instead of normotensive following the administration of an antihypertensive agent). 

Therapeutic uses Thiazide diuretics decrease blood pressure in both the supine and standing positions postural hypotension is rarely observed, except in elderly, volume-depleted patients. These agents counteract the sodium and water retention observed with other agents used in the treatment of hypertension (for example, hydralazine). Thiazides are therefore useful in combination therapy with a variety of other antihypertensive agents including (3-blockers and ACE inhibitors. Thiazide diuretics are particularly useful in the treatment of black or elderly patients, and in those with chronic renal disease. Thiazide diuretics are not effective in patients with inadequate kidney function (creatinine clearance less than 50 mls/min). Loop diuretics may be required in these patients. 

It should be remembered that hypertension in patients with renal dysfunction can be particularly difficult to treat, and many patients require more than one antihypertensive agent in order to control their blood pressure. There is some guidance provided by the Renal Association in their Clinical Guidelines document as to choice of therapeutic agent ... 

In conclusion, the incorporation of an acetylenic moiety into a benzylamine structure conferred completely novel biochemical and therapeutic properties on an otherwise inert phenylalkylamine. Outstanding in this respect are the potent MAO-inhibitory, antihypertensive, and antidepressant effects of this new drug. The potent autonomic side effects normally encountered with the ganglionic blocking type antihypertensive agents are much less pronounced with this drug and a definite advance has been scored toward achieving selectivity of action. 

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